The reaction center chlorophylls a (Chla) of photosystem II (PSII) are composed of six Chla molecules including the special pair Chla P-D1/P-D2 harbored by the D1/D2 heterodimer. They serve as the ultimate electron abstractors for water oxidation in the oxygen-evolving Mn4CaO5 cluster. Using the PSII crystal structure analyzed at 1.9 angstrom resolution, the redox potentials of P-D1/center dot P-D2 for one-electron oxidation (E-m) were calculated by considering all PSII subunits and the protonation pattern of all titratable residues. The Em(Chla) values were calculated to be 1015-1132 mV for P-D1 and 1141-1201 mV for P-D2, depending on the protonation state of the Mn4CaO5 cluster. The results showed that Em(P-D1) was lower than E-m(P-D2) P-D2 favoring localization of the charge of the cationic state more on P-D1. The P-D1(center dot+)/P-D2(center dot+) charge ratio determined by the large-scale QM/MM calculations with the explicit PS II protein environment yielded a P-D1(center dot+)/P-D2(center dot+) ratio of similar to 80/similar to 20, which was found to be due to the asymmetry in electrostatic characters of several conserved D1/D2 residue pairs that cause the E-m(P-D1)/E-m(P-D2) difference, e.g., Dl -Asn181/D2-Argl 80, D1-Asn298/D2-Arg294, D1-Asp61/D2-His61, D1-Glu189/D2-Phe188, and D1-Asp170/D2-Phe169. The larger P-D1(center dot+) population than P-D2(center dot+) appears to be an inevitable fate of the intact PSII that possesses water oxidation activity.